Hyperphosphatemia is a serious and chronic medical condition in end-stage renal diseases. Although it is possible to increase the elimination of phosphate from the plasma in dialysis patient, this approach is severely limited by the fact that transfer of phosphate from the blood cells into plasma is the rate-limiting step (Pohlmeier and Vienken, Phosphate removal and hemodialysis conditions. Kidney Int. Suppl. 78:S190-194 (2001)). Therefore, a more promising route of treating phosphate overload is to decrease the absorption of phosphate. Phosphate is transported into the intestinal cells via a phosphate-sodium co-transporter, and transported across the basolateral membrane into the blood via a yet to be identified pathway (Murer et. al., Molecular aspects in the regulation of renal inorganic phosphate reabsorption: the type IIa sodium/inorganic phosphate co-transporter as the key player. Curr. Opin. Nephrol. Hypertens. 10:555-561 (2001)). The phosphate-sodium cotransporter is stimulated by 1,25-dihydroxycholecalciferol, an active metabolite of vitamin D, but the mechanism of this action is not entirely clear. Because phosphate is taken up by carrier-mediated pathways, the rate of absorption may not increase linearly with the concentration.
Presently, the therapy for managing phosphate absorption is through the use of precipitation agents such as aluminum, calcium (Malluche et. al., Hyperphosphatemia: pharmacologic intervention yesterday, today and tomorrow. Clin. Nephrol. 54:309-317 (2000)) and other heavy metal ions such as lanthanum, and a polymer-like materials such as sevelamer HCl, (a non-aluminum, non-calcium containing hydrogel or Renagel®) (Gallieni et. al., Sevelamer reduces calcium load and maintains a low calcium-phosphorus ion product in dialysis patients. J Nephrol. 14:176-183 (2001)). These agents have been shown to be beneficial but better agents are yet to be developed, because the available drugs are only partially effective.